Catalytic reductive coupling of enone, acrylate, or vinyl heteroaromatic pronucleophiles with carbonyl or imine partners offers an alternative to base-mediated enolization in aldol-and Mannich-type reactions. In this review, direct catalytic reductive aldol and Mannich reactions are exhaustively catalogued on the basis of metal or organocatalyst. Stepwise processes involving enone conjugate reduction to form discrete enol or (metallo)enolate derivatives followed by introduction of carbonyl or imine electrophiles and aldol reactions initiated via enone conjugate addition are not covered.
Crystallographic characterization
of RuX(CO)(η3-C3H5)(JOSIPHOS),
where X = Cl, Br, or I, reveals
a halide-dependent diastereomeric preference that defines metal-centered
stereogenicity and, therefrom, the enantioselectivity of C−C
coupling in ruthenium-catalyzed anti-diastereo- and
enantioselective C−C couplings of primary alcohols with 1-aryl-1-propynes
to form products of carbonyl anti-(α-aryl)allylation.
Computational studies reveal that a non-classical hydrogen bond between
iodide and the aldehyde formyl CH bond stabilizes the favored transition
state for carbonyl addition. An improved catalytic system enabling
previously unattainable transformations was developed that employs
an iodide-containing precatalyst, RuI(CO)3(η3-C3H5), in combination with trifluoroethanol,
as illustrated by the first enantioselective ruthenium-catalyzed C−C
couplings of ethanol to form higher alcohols.
Iodide-bound ruthenium-JOSIPHOS complexes catalyze the redox-neutral CÀ C coupling of primary alcohols with methylallene (1,2-butadiene) or 1,3-butadiene to form products of anti-crotylation with good to excellent levels of diastereo-and enantioselectivity. Distinct from other methods, direct crotylation of primary alcohols in the presence of unprotected secondary alcohols is possible, enabling generation of spirastrellolide B (C9-C15) and leucascandrolide A (C9-C15) substructures in significantly fewer steps than previously possible.
The
first catalytic enantioselective ruthenium-catalyzed carbonyl
reductive couplings of allene pronucleophiles is described. Using
an iodide-modified ruthenium-BINAP-catalyst and O-benzhydryl alkoxyallene 1a, carbonyl (α-alkoxy)allylation
occurs from the alcohol or aldehyde oxidation level to form enantiomerically
enriched syn-sec,tert-diols. Internal
chelation directs intervention of (Z)-σ-alkoxyallylruthenium
isomers, which engage in stereospecific carbonyl addition.
The
use of alkynes as vinylmetal pronucleophiles in intermolecular
enantioselective metal-catalyzed carbonyl and imine reductive couplings
to form allylic alcohols and amines is surveyed. Related hydrogen
autotransfer processes, wherein alcohols or amines serve dually as
reductants and carbonyl or imine proelectrophiles, also are cataloged,
as are applications in target-oriented synthesis. These processes
represent an emerging alternative to the use of stoichiometric vinylmetal
reagents or Nozaki–Hiyama–Kishi (NHK) reactions in carbonyl
and imine alkenylation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.